Hematopoietic stem cell transplant (HSCT) can cure thalassemia major (TM), but only 30% of the patients have a matched sibling donor. Alternative donors, including unrelated donors, cord blood, and parental donors, have continuously improved the results of HSCT in leukemia in the last decades. Therefore, HSCT from alternative donors were gradually applied to thalassemia. Our previous encouraging single-center results of the "the NF-08-TM" protocol in unrelated donor transplant in TM patients have published in Blood in 2012. 1 Considering the limitations of our single-center study, we subsequently carried out a multicenter collaboration using the NF-08-TM protocol. 1 Here we report the long-term results from the multi-center study. A total of 486 consecutive HSCT from four pediatric centers in China between July 2011 and June 2016 using the NF-08-TM protocol were analyzed. The ratio of male to female was 309 to 177 with a median age of 6 years (range, 2-23 years). Most patients were classified in group two according to the criteria of the NF-08-TM protocol. Patients were classified into two groups according to human leukocyte antigen (HLA-A,HLA-B, HLA-C and HLA-DRB1) matching, that is,10/10 matched group (n = 428, 88.1%) and 9/10 (n = 58, 11.9%). One hundred and nine-three patients underwent sibling donor HSCT (190 matches and three mismatches); 212 unrelated donor HSCT (173 matches and 39 mismatches), 35 parent donor HSCT (19 matches and 16 mismatches) and 46 sibling cord blood transplants (all matched). Except for cord blood transplant, peripheral blood stem cells were used as a stem cell source in the current cohort. A constant mononuclear cell dose

Background: Unrelated cord blood (UCB) transplant (UCBT) is not recommended in patients with thalassemia major (TM) so far. Post-transplant (PT) Cyclophosphamide (PTCy) with long pre-transplant immunosuppression therapy have improved haploidentical peripheral blood (PB) stem cell transplant (haplo-SCT) survival in TM patients but with 2/31 primary rejection. So, we designed a novel dual transplantation of UCBT following haplo-SCTwith PTCy(NF-14-TM-CT protocol). Aim:To improve results of haplo-SCT and UCBT in patients with TM. Patients and method: NF-14-TM -CT protocol was termed as double-insurance dual transplantsincluding a haplo-SCT and an UCBT, in which conditioning regimen consisted of ATG (at -10 to -8 day), Cy (-7), Fludarabine (-6 to -2), Busulfan (-6 to -4) Thiotepa (-3), haplo-PB (0), PTCy (+3, +4) and UCB (+6). PTCy serve as GVHD prophylaxes after haplo-SCT and as conditioning before UCBT. In total 131 patients with TM from three pediatric center in China received NF-14-TM-CT protocolfrom June, 2014 to April, 2019, with a median follow-up of 13 (2-59) months and a median age of 8 (3.5-17) years. Results Final haplo-PB engrafted(group1)in 76 patients with mean PBSC-MNCof 22.49 (±5.36) x108/kgand UCB nuclear cells (NC) of 5.95 (±3.39) x107/kg and final UCB engrafted (group 2) in 55 patients with mean PBSC-MNC of 21.78 (±5.68) x108/kg and mean UCB-NC of. 5.43 (±2.32) x107/kg. The 4-year overall survival (OS), thalassemia-free survival (TFS), graft rejection (GR), and transplant related mortality (TRM) were 97.6%, 96.0%, 1.5%, and 2.4%, respectively (Fig. A), in total. The corresponding rates for group 1 were 98.3%, 96.9%, 1.7% and 1.8% and for group 2 were 95.5%, 93.8%, 4.5% and 1.4%, respectively. No statistic significant difference was found in OS, TFS, GR and TRM, respectively, when comparing group 1 with group 2 (Fig. B. C, D, E).The incidence of grade II-IV acute GVHD, III-IV acute GVHD, mild chronic GVHD, moderate/severe chronic GVHD, VOD, PT cystitisand PT hemolysis of the entire cohort was 16.8%, 6.87%, 9.92%, 1.52%, 4.60%, 31.3% and 14.5, respectively. Summary:Current study proved that the novel CT improved the results of haplo-SCT and UCBT in patients with TM. Disclosures Wing: Miltenyi Biotec: Employment.

Current study analyses the effect of splenectomy on outcomes of hematopoietic stem cell transplantation (HSCT) for patients with β-thalassemia major (TM). Twenty-two class II and III (according to Nanfang’s criteria, see Blood, 2012;120 (19): 3875-3881) patients with TM had a pre-transplant splenectomy. The outcomes of the 22 transplants were compared with 193 transplants in class II and III patients between Aug. 2008 and Dec. 2013. Patients in the splenectomy group were older (8.9±5.0 vs. 6.0±3.5 year old; p=0.001) and class III patients were more (8/22 vs. 10/193, p=0.001) than non-splenectomy. In splenectomy group 10 patients received graft from HLA matched sibling, 9 from unrelated donors and 3 from haploidentical parents plus unrelated cord blood, respectively. In non-splenectomy group 82 patients received graft from matched sibling and 121 from unrelated donors, respectively. 213 cases engrafted in 4 weeks, Splenectomized patients had a significantly shorter time to absolute neutrophil count >500/mm3 (14.5±5.2 vs 19±4.2 days p=0.001). There were no significantly different at time to platelet >2000/mm3 (16.2±5.8 vs 16.1±5.3 days, p=0.415) and hemoglobin >80g/L (15.3±4.8 vs 13.1±5.3 days p=0.135). Secondary rejection occurred in 2 patients (at 3rd month and 4th month post transplantation, respectively) in splenectomy group, but rescued successfully by second transplants from unrelated donor one year later and from haploidentical parent two years later, respectively. The patients received graft from father, one died of complications of VOD; other died of lung infection on forty-five days post transplantation. Two patients rejected their grafts in non-splenectomy group. The mean RBC transfusion was 4u (0u-12u). The mean platelet transfusion in splenectomy group had reduced (4.4±4.5 vs 7.1±4.8 units p=0.016), with 17 patients transfused less than 6u Platelet. The incidence of acute and chronic GVHD, late infections were rare and not significantly different between the two groups. No patients died of infection due to splenectomy. Patients underwent HSCT after splenectomy had a high rate of OS (95.5% vs 92.8% p=0.001). Although TFS was lower in splenectomy group than non-splenectomy group (88.5% vs 92.3% p=0.001), this may be due to more older, class III patients and higher rate of rejection (2/22 vs 2/193). Conclusion, our study showed pre-transplant splenectomy patients with β-thalassemia major was associated with faster engraftment and decreased require of platelet and bloodtransfusion support. Disclosures No relevant conflicts of interest to declare.